tolvaptan (Rx)

Brand and Other Names:Samsca, Jynarque
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet (Samsca)

  • 15mg
  • 30mg

tablet (Jynarque)

  • 15mg
  • 30mg
  • 45mg
  • 60mg
  • 90mg

Hyponatremia

Samsca only

Indicated for adults with clinically significant euvolemic or hypervolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure, cirrhosis, and SIADH

Initial: 15 mg PO qDay

Maintenance: May increase to 30 mg qDay after at least 24 hr to achieve the optimal serum sodium level; not to exceed 60 mg/day

Not to exceed 30 days of treatment

Polycystic Kidney Disease

Jynarque only

Indicated to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD)

Initial: 45 mg PO taken on waking and 15 mg taken 8 hr later (ie, 60 mg/day)

Titrate to 60 mg plus 30 mg, then to 90 mg plus 30 mg per day if tolerated, with at least weekly intervals between titrations

Patients may down-titrate based on tolerability

Encourage patients to drink enough water to avoid thirst or dehydration

Dosage Modifications

Renal impairment

  • CrCl 10-79 mL/min: No dosage adjustment required
  • CrCl <10 mL or dialysis: Not recommended; drug effects on serum sodium levels are likely lost at very low levels of renal function
  • Anuria: Contraindicated; no benefit expected

Hepatic impairment

  • Moderate and severe hepatic impairment do not affect exposure to tolvaptan to a clinically relevant extent
  • Underlying liver disease: Avoid use

Strong CYP3A inhibitors

  • Coadministration with strong CYP3A inhibitors: Contraindicated; causes a marked (5-fold) increase in tolvaptan exposure

Moderate CYP3A inhibitors (Samsca)

  • Not studied; prescribing information recommends avoiding coadministration

Moderate CYP3A inhibitors (Jynarque)

  • Reduce the dose if coadministered with moderate CYP3A inhibitor; consider further reductions if patients cannot tolerate the reduced dose
  • Interrupt temporarily for short-term therapy with moderate CYP3A inhibitors if the recommended reduced doses are not available
  • Dose reduction with moderate CYP3A inhibitors
    • Taking 90 mg and 30 mg: Reduce to 45 mg and 15 mg
    • Taking 60 mg and 30 mg: Reduce to 30 mg and 15 mg
    • Taking 45 mg and 15 mg: Reduce to 15 mg and 15 mg

Potent CYP3A inducers

  • Coadministration with potent CYP3A inducers: Monitor and adjust tolvaptan dose accordingly; potent inducers reduce tolvaptan plasma concentrations by 85%

P-gp inhibitors

  • Coadministration with P-gp inhibitors: Monitor; tolvaptan dose may need to be reduced

Dosing Considerations

Limitations of use (Samsca)

  • Patients should be hospitalized for initiation and reinitiation of therapy to evaluate the therapeutic response and because too-rapid correction of hyponatremia can cause osmotic demyelination
  • Do not use in patients requiring intervention to raise serum sodium urgently to prevent or to treat serious neurological symptoms
  • It has not been established that raising serum sodium with tolvaptan provides a symptomatic benefit to patients
  • Monitor serum sodium

Jynarque

  • Monitoring to mitigate risk of liver injury
    • Perform blood testing for ALT, AST, and bilirubin prior to initiating, at 2 and 4 weeks after initiation, monthly for 18 months, and q3Months thereafter
    • Monitor for concurrent symptoms that may indicate liver injury

Safety and efficacy not established

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Interactions

Interaction Checker

and tolvaptan

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            Contraindicated (1)

            • itraconazole

              itraconazole will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Larger doses of strong CYP3A4 inhibitors may produce larger increases in tolvaptan exposure. Concomitant use of tolvaptan with strong CYP3A4 inhibitors is contraindicated.

            Serious - Use Alternative (98)

            • abametapir

              abametapir will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • amobarbital

              amobarbital will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • apalutamide

              apalutamide will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

            • aprepitant

              aprepitant will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • armodafinil

              armodafinil will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • artemether/lumefantrine

              artemether/lumefantrine will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • atazanavir

              atazanavir will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • bosentan

              bosentan will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • bosutinib

              tolvaptan increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • budesonide

              budesonide will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • butabarbital

              butabarbital will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • butalbital

              butalbital will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • carbamazepine

              carbamazepine will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • chloramphenicol

              chloramphenicol will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • cimetidine

              cimetidine will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • clarithromycin

              clarithromycin will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • cobicistat

              cobicistat will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • conivaptan

              conivaptan will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • cortisone

              cortisone will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • cyclosporine

              cyclosporine will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • dabrafenib

              dabrafenib will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • darifenacin

              darifenacin will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • darunavir

              darunavir will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • dasatinib

              dasatinib will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • dexamethasone

              dexamethasone will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • DHEA, herbal

              DHEA, herbal will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • diltiazem

              diltiazem will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. In patients taking concomitant moderate CYP3A inhibitors, reduce tolvaptan dose (see Prescribing Information). Consider further reductions if patients cannot tolerate the reduced dose. Interrupt tolvaptan temporarily for short term therapy with moderate CYP3A inhibitors if the recommended reduced doses are not available.

            • dronedarone

              dronedarone will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • efavirenz

              efavirenz will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • enzalutamide

              enzalutamide will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erdafitinib

              erdafitinib will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration unavoidable, separate administration by at least 6 hr before or after administration of P-gp substrates with narrow therapeutic index.

            • erythromycin base

              erythromycin base will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • etravirine

              etravirine will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • fexinidazole

              fexinidazole will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • fluconazole

              fluconazole will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • fludrocortisone

              fludrocortisone will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • fluvoxamine

              fluvoxamine will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • fosamprenavir

              fosamprenavir will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • grapefruit

              grapefruit will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • griseofulvin

              griseofulvin will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • hydrocortisone

              hydrocortisone will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • idelalisib

              idelalisib will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

            • indinavir

              indinavir will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • isoniazid

              isoniazid will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ivosidenib

              ivosidenib will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • ketoconazole

              ketoconazole will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • lapatinib

              lapatinib will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • lasmiditan

              lasmiditan increases levels of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • lonafarnib

              lonafarnib will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

            • lopinavir

              lopinavir will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • lumefantrine

              lumefantrine will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • marijuana

              marijuana will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • methylprednisolone

              methylprednisolone will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • metronidazole

              metronidazole will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • miconazole vaginal

              miconazole vaginal will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • mifepristone

              mifepristone will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • modafinil

              modafinil will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • nafcillin

              nafcillin will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • nefazodone

              nefazodone will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • nelfinavir

              nelfinavir will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • nevirapine

              nevirapine will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • nifedipine

              nifedipine will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • nilotinib

              nilotinib will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • pentobarbital

              pentobarbital will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • phenobarbital

              phenobarbital will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • phenytoin

              phenytoin will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • pomalidomide

              tolvaptan increases levels of pomalidomide by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • posaconazole

              posaconazole will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • prednisone

              prednisone will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • primidone

              primidone will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • quinidine

              quinidine will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ribociclib

              ribociclib will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • rifabutin

              rifabutin will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • rifampin

              rifampin will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • rifapentine

              rifapentine will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • ritonavir

              ritonavir will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • rufinamide

              rufinamide will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • saquinavir

              saquinavir will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • secobarbital

              secobarbital will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • sotorasib

              sotorasib will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.

            • St John's Wort

              St John's Wort will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • tepotinib

              tepotinib will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

            • tipranavir

              tipranavir will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • topiramate

              topiramate will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • topotecan

              tolvaptan will increase the level or effect of topotecan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Product labeling for PO topotecan recommends avoiding concomitant use of P-gp inhibitors; the interaction with IV topotecan may be less severe but is still likely of clinical significance

            • triamcinolone acetonide injectable suspension

              triamcinolone acetonide injectable suspension will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • tucatinib

              tucatinib will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • verapamil

              verapamil will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • voriconazole

              voriconazole will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • voxelotor

              voxelotor will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

            • zafirlukast

              zafirlukast will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            Monitor Closely (193)

            • acebutolol

              acebutolol and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • aceclofenac

              aceclofenac and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • acemetacin

              acemetacin and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • albuterol

              tolvaptan increases and albuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • amikacin

              tolvaptan will increase the level or effect of amikacin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • amiloride

              amiloride and tolvaptan both increase serum potassium. Modify Therapy/Monitor Closely.

            • amiodarone

              amiodarone will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • amitriptyline

              tolvaptan will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • arformoterol

              tolvaptan increases and arformoterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • aspirin

              aspirin and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • aspirin rectal

              aspirin rectal and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • aspirin/citric acid/sodium bicarbonate

              aspirin/citric acid/sodium bicarbonate and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • atenolol

              atenolol and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • atorvastatin

              atorvastatin will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              tolvaptan will increase the level or effect of atorvastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • azithromycin

              azithromycin will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • bazedoxifene/conjugated estrogens

              tolvaptan will increase the level or effect of bazedoxifene/conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • bendroflumethiazide

              tolvaptan increases and bendroflumethiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • berotralstat

              berotralstat will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • betaxolol

              betaxolol and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • bisoprolol

              bisoprolol and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • bosutinib

              bosutinib increases levels of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • budesonide

              tolvaptan will increase the level or effect of budesonide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • bumetanide

              tolvaptan increases and bumetanide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • candesartan

              candesartan and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • captopril

              tolvaptan, captopril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hyperkalemia.

            • carbenoxolone

              tolvaptan increases and carbenoxolone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • carvedilol

              carvedilol and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • celecoxib

              celecoxib and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • celiprolol

              celiprolol and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • chlorothiazide

              tolvaptan increases and chlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • chlorthalidone

              tolvaptan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • choline magnesium trisalicylate

              choline magnesium trisalicylate and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • clarithromycin

              clarithromycin will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • clobetasone

              tolvaptan will increase the level or effect of clobetasone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • clotrimazole

              clotrimazole will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • conjugated estrogens

              tolvaptan will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • conjugated estrogens, vaginal

              tolvaptan will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • cortisone

              tolvaptan will increase the level or effect of cortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • crizotinib

              crizotinib increases levels of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • cyclopenthiazide

              tolvaptan increases and cyclopenthiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • cyclosporine

              cyclosporine will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              tolvaptan will increase the level or effect of cyclosporine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • deferasirox

              deferasirox will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • deflazacort

              tolvaptan will increase the level or effect of deflazacort by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • dexamethasone

              tolvaptan will increase the level or effect of dexamethasone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • diclofenac

              diclofenac and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • diflunisal

              diflunisal and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • digoxin

              tolvaptan will increase the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              digoxin and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • dobutamine

              tolvaptan increases and dobutamine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • docetaxel

              tolvaptan will increase the level or effect of docetaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • dopexamine

              tolvaptan increases and dopexamine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dronedarone

              dronedarone will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • drospirenone

              drospirenone and tolvaptan both increase serum potassium. Modify Therapy/Monitor Closely.

            • elagolix

              elagolix will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              elagolix decreases levels of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • eliglustat

              eliglustat increases levels of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.

            • encorafenib

              encorafenib, tolvaptan. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

            • ephedrine

              tolvaptan increases and ephedrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • epinephrine

              tolvaptan increases and epinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • epinephrine racemic

              tolvaptan increases and epinephrine racemic decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • eprosartan

              eprosartan and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • erythromycin base

              erythromycin base will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • esmolol

              esmolol and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • estradiol

              tolvaptan will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • estrogens conjugated synthetic

              tolvaptan will increase the level or effect of estrogens conjugated synthetic by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • estrogens esterified

              tolvaptan will increase the level or effect of estrogens esterified by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • estropipate

              tolvaptan will increase the level or effect of estropipate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ethacrynic acid

              tolvaptan increases and ethacrynic acid decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • etodolac

              etodolac and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • felodipine

              felodipine will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • fenoprofen

              fenoprofen and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • fludrocortisone

              tolvaptan will increase the level or effect of fludrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • flurbiprofen

              flurbiprofen and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • formoterol

              tolvaptan increases and formoterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • furosemide

              tolvaptan increases and furosemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • gentamicin

              tolvaptan will increase the level or effect of gentamicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              tolvaptan increases and gentamicin decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • glecaprevir/pibrentasvir

              glecaprevir/pibrentasvir will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • hydrochlorothiazide

              tolvaptan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • hydrocortisone

              tolvaptan will increase the level or effect of hydrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ibuprofen

              ibuprofen and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • ibuprofen IV

              ibuprofen IV and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • indapamide

              tolvaptan increases and indapamide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • indinavir

              indinavir will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              tolvaptan will increase the level or effect of indinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • indomethacin

              indomethacin and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • irbesartan

              irbesartan and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • irinotecan liposomal

              tolvaptan will increase the level or effect of irinotecan liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • isoproterenol

              tolvaptan increases and isoproterenol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • istradefylline

              istradefylline will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

              istradefylline will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.

            • itraconazole

              tolvaptan will increase the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ivacaftor

              ivacaftor increases levels of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • ivermectin

              tolvaptan will increase the level or effect of ivermectin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ketoconazole

              ketoconazole will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ketoprofen

              ketoprofen and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • ketorolac

              ketorolac and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • ketorolac intranasal

              ketorolac intranasal and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • labetalol

              labetalol and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • lapatinib

              lapatinib will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • levalbuterol

              tolvaptan increases and levalbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • lomitapide

              lomitapide increases levels of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing dose when used concomitantly with lomitapide.

            • lonafarnib

              lonafarnib will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.

            • loperamide

              tolvaptan will increase the level or effect of loperamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • loratadine

              loratadine will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • lorlatinib

              lorlatinib will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lornoxicam

              lornoxicam and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • losartan

              losartan and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • lovastatin

              lovastatin will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              tolvaptan will increase the level or effect of lovastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • maraviroc

              tolvaptan will increase the level or effect of maraviroc by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • meclofenamate

              meclofenamate and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • mefenamic acid

              mefenamic acid and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • meloxicam

              meloxicam and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • mestranol

              tolvaptan will increase the level or effect of mestranol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • metaproterenol

              tolvaptan increases and metaproterenol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • methyclothiazide

              tolvaptan increases and methyclothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

            • methylprednisolone

              tolvaptan will increase the level or effect of methylprednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • metolazone

              tolvaptan increases and metolazone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • metoprolol

              metoprolol and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • mitotane

              mitotane decreases levels of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

            • nabumetone

              nabumetone and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • nadolol

              nadolol and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • naproxen

              naproxen and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • nebivolol

              nebivolol and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • nefazodone

              nefazodone will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nelfinavir

              tolvaptan will increase the level or effect of nelfinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • neomycin PO

              tolvaptan will increase the level or effect of neomycin PO by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nicardipine

              nicardipine will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nifedipine

              nifedipine will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nilotinib

              nilotinib will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • norepinephrine

              tolvaptan increases and norepinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • olmesartan

              olmesartan and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • oxaprozin

              oxaprozin and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • paclitaxel

              tolvaptan will increase the level or effect of paclitaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • paclitaxel protein bound

              tolvaptan will increase the level or effect of paclitaxel protein bound by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • paliperidone

              tolvaptan will increase the level or effect of paliperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • parecoxib

              parecoxib and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • paromomycin

              tolvaptan will increase the level or effect of paromomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • penbutolol

              penbutolol and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • phenobarbital

              phenobarbital will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • phenytoin

              phenytoin will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • pindolol

              pindolol and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • pirbuterol

              tolvaptan increases and pirbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • piroxicam

              piroxicam and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • ponatinib

              ponatinib increases levels of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • posaconazole

              tolvaptan will increase the level or effect of posaconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • potassium acid phosphate

              potassium acid phosphate and tolvaptan both increase serum potassium. Modify Therapy/Monitor Closely.

            • potassium chloride

              potassium chloride and tolvaptan both increase serum potassium. Modify Therapy/Monitor Closely.

            • potassium citrate

              potassium citrate and tolvaptan both increase serum potassium. Modify Therapy/Monitor Closely.

            • prednisolone

              tolvaptan will increase the level or effect of prednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • prednisone

              tolvaptan will increase the level or effect of prednisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • propranolol

              propranolol and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • quercetin

              quercetin will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ranolazine

              ranolazine will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • rifampin

              rifampin will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • risperidone

              tolvaptan will increase the level or effect of risperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ritonavir

              ritonavir will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              tolvaptan will increase the level or effect of ritonavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • rucaparib

              rucaparib will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • sacubitril/valsartan

              sacubitril/valsartan and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • salicylates (non-asa)

              salicylates (non-asa) and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • salmeterol

              tolvaptan increases and salmeterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • salsalate

              salsalate and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • saquinavir

              tolvaptan will increase the level or effect of saquinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • sarecycline

              sarecycline will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

            • silodosin

              tolvaptan will increase the level or effect of silodosin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • simvastatin

              simvastatin will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • sirolimus

              sirolimus will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              tolvaptan will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • sotalol

              sotalol and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • spironolactone

              spironolactone and tolvaptan both increase serum potassium. Modify Therapy/Monitor Closely.

            • St John's Wort

              St John's Wort will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • stiripentol

              stiripentol, tolvaptan. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

              stiripentol will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.

            • streptomycin

              tolvaptan will increase the level or effect of streptomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • succinylcholine

              succinylcholine and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • sulfasalazine

              sulfasalazine and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • sulindac

              sulindac and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • tacrolimus

              tacrolimus will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              tolvaptan will increase the level or effect of tacrolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • tazemetostat

              tazemetostat will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tecovirimat

              tecovirimat will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            • telmisartan

              telmisartan and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • terbutaline

              tolvaptan increases and terbutaline decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • timolol

              timolol and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • tobramycin

              tolvaptan will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • tolfenamic acid

              tolfenamic acid and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • tolmetin

              tolmetin and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • torsemide

              tolvaptan increases and torsemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • trazodone

              trazodone will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • triamterene

              triamterene and tolvaptan both increase serum potassium. Modify Therapy/Monitor Closely.

            • tucatinib

              tucatinib will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

            • valsartan

              valsartan and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • vemurafenib

              vemurafenib increases levels of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • verapamil

              verapamil will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Coadministration of moderate CYP 3A inhibitors, such as Verapamil with Tolvaptan should be avoided.

            • vinblastine

              tolvaptan will increase the level or effect of vinblastine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • vincristine

              tolvaptan will increase the level or effect of vincristine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • vincristine liposomal

              tolvaptan will increase the level or effect of vincristine liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            Minor (7)

            • aliskiren

              tolvaptan will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • alvimopan

              tolvaptan will increase the level or effect of alvimopan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • ambrisentan

              tolvaptan will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • armodafinil

              tolvaptan will increase the level or effect of armodafinil by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • fexofenadine

              tolvaptan will increase the level or effect of fexofenadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • loratadine

              tolvaptan will increase the level or effect of loratadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • noni juice

              noni juice and tolvaptan both increase serum potassium. Minor/Significance Unknown.

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            Adverse Effects

            >10%

            Samsca

            • Nausea (21%)
            • Thirst (16%)
            • Dry mouth (13%)
            • Pollakiuria (4-11%)
            • Urinary frequency/output increased (11%)

            Jynarque

            • Increased urination (69.5%)
            • Thirst (63.7%)
            • Dry mouth (16%)
            • Fatigue (13.6%)
            • Diarrhea (13.3%)
            • Dizziness (11.3%)

            1-10%

            Samsca

            • GI bleeding with preexisting cirrhosis (10%)
            • Weakness (9%)
            • Constipation (7%)
            • Hyperglycemia (6%)
            • Anorexia (4%)
            • Pyrexia (4%)

            Jynarque

            • Dyspepsia (7.9%)
            • Decreased appetite (7.2%)
            • Abdominal distension (4.9%)
            • Dry skin (4.9%)
            • Rash (4.2%)
            • Hyperuricemia (3.9%)
            • Palpitations (3.5%)

            Postmarketing Reports

            Neurologic: Osmotic demyelination syndrome

            Investigations: Hypernatremia

            Immune system disorders: Hypersensitivity reactions including anaphylactic shock and rash

            Hepatobiliary disorders: Liver failure requiring transplantation

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            Warnings

            Black Box Warnings

            Samsca

            • Initiate or reinitiate only in a hospital where serum sodium level can be monitored closely
            • Too-rapid correction of hyponatremia (eg, >12 mEq/L/24 hr) can cause osmotic demyelination resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma, and death
            • In susceptible patients, including those with severe malnutrition, alcoholism, or advanced liver disease, slower rates of correction may be advisable
            • Not for use for ADPKD because of risk of hepatoxicity; tolvaptan (Jynarque) is specifically indicated for ADPKD

            Jynarque

            • Can cause serious and potentially fatal liver injury; acute liver failure requiring liver transplantation reported
            • Measure ALT, AST and bilirubin before initiating treatment, at 2 weeks and 4 weeks after initiation, monthly for the first 18 months ,and q3Months thereafter
            • Prompt action in response to laboratory abnormalities, signs, or symptoms indicative of hepatic injury can mitigate, but not eliminate, the risk of serious hepatotoxicity
            • Because of the risks of serious liver injury, available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS) called the Jynarque REMS Program; additional information is available at www.jynarquerems.com or by telephone at 1-877-726-7220

            Contraindications

            Concomitant use of strong CYP3A inhibitors

            Hypersensitivity (eg, anaphylactic shock, generalized rash)

            Anuria

            Inability of patient to sense or appropriately respond to thirst

            Hypovolemic hyponatremia

            Samsca

            • Use in patients with ADPKD outside of FDA-approved REMS (see Black Box Warnings)
            • Urgent need to raise serum sodium acutely

            Jynarque

            • History, signs, or symptoms of significant liver impairment or injury; this contraindication does not apply to uncomplicated polycystic liver disease
            • Uncorrected abnormal blood sodium concentrations
            • Uncorrected urinary outflow obstruction

            Cautions

            Hypernatremia, hypovolemia, and/or dehydration may occur; encourage patient to drink whenever thirsty

            Patients with partial obstruction of urinary outflow, patients with prostatic hypertrophy or impairment of micturition, have increased risk of developing acute retention

            Can cause serious and potentially fatal liver injury; acute liver failure requiring liver transplantation reported; discontinue if laboratory abnormalities or signs or symptoms of liver injury are evident (see Black Box Warnings); limit duration of therapy to 30 days; avoid use in patients with underlying liver disease, including cirrhosis, because ability to recover from liver injury may be impaired

            In patients who develop medically significant signs or symptoms of hypovolemia, interrupt or discontinue therapy and provide supportive care with careful management of vital signs, fluid balance and electrolytes; fluid restriction during therapy may increase risk of dehydration and hypovolemia; patients receiving therapy should continue ingestion of fluid in response to thirst

            Osmotic demyelination syndrome

            • Osmotic demyelination syndrome is a risk associated with too-rapid correction of hyponatremia (see Black Box Warnings)
            • In susceptible patients, including those with severe malnutrition, alcoholism or advanced liver disease, slower rates of correction may be advisable
            • In patients who develop too rapid a rise in serum sodium, discontinue or interrupt treatment and consider administration of hypotonic fluid; fluid restriction during first 24 hr of therapy may increase likelihood of overly-rapid correction of serum sodium, and should generally be avoided; co-administration of diuretics also increases risk of too rapid correction of serum sodium; such patients should undergo close monitoring of serum sodium
            • Patients with symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice should discontinue treatment

            Drug interaction overview

            • Hypertonic saline: Concomitant use not recommended
            • Diuretics: Increases risk for dehydration
            • P-gp inhibitors: Monitor; dose reduction may be required
            • Drugs that increase serum potassium: Tolvaptan may have additive hyperkalemic effects if coadministered
            • P-gp substrates: Tolvaptan may increase AUC and Cmax of P-gp substrates
            • OATP1B1/3 and OAT3 substrates: Avoid concomitant use; tolvaptan may increase plasma concentrations of these substrates
            • BCRP substrates: Avoid concomitant use; tolvaptan is an inhibitor of BCRP
            • V2-receptor agonists: Avoid concomitant use; tolvaptan, a V2-antagonist, interferes with V2-agonist activity (eg, desmopressin [dDAVP])
            • CYP3A
              • Tolvaptan is a substrate of CYP3A
              • CYP3A inhibitors can lead to a marked increase in tolvaptan concentrations
              • Coadministration with strong CY3A inhibitors: Contraindicated
              • Coadministration with moderate CYP3A inhibitors: Avoid (Samsca); modify dose (Jynarque)
              • Coadministration with CYP3A inducers: Monitor; dosage increase may be required
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            Pregnancy & Lactation

            Pregnancy

            Available data are insufficient to determine if there is a drug-associated risk of adverse developmental outcomes

            Animal studies

            • In embryo-fetal development studies, pregnant rats and rabbits received oral tolvaptan during organogenesis
            • At maternally nontoxic doses, tolvaptan did not cause any developmental toxicity in rats or in rabbits at exposures approximately 4- and 1-times, respectively, the human exposure at the maximum recommended human dose (MRHD) of 90/30 mg; however, effects on embryo-fetal development occurred in both species at maternally toxic doses

            Lactation

            Data are not available on the presence of tolvaptan in human milk, the effects on the breastfed infant, or the effects on milk production

            Tolvaptan is present in rat milk

            Because of the potential for serious adverse reactions, including liver toxicity, electrolyte abnormalities (eg, hypernatremia), hypotension, and volume depletion in breastfed infants, advise women not to breastfeed during treatment

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Selective vasopressin V2-receptor antagonist that causes an increase in urine water excretion that results in an increase in free water clearance (aquaresis), a decrease in urine osmolality, and a resulting increase in serum sodium concentration

            Absorption

            Absolute bioavailability: Unknown; at least 40% of the dose is absorbed as tolvaptan or metabolites

            Peak plasma concentration: 2-4 hr

            Distribution

            Protein bound: 99%

            Vd: 3 L/kg

            Metabolism

            Eliminated entirely by nonrenal routes and mainly, if not exclusively, metabolized by CYP3A

            Elimination

            Half-life, terminal: 12 hr

            Clearance: 4 mL/min/kg

            Excretion: Nonrenal

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            Administration

            Oral Administration

            May take with or without food

            Samsca

            • Do not exceed 30 days of administration to minimize risk of liver injury
            • Following discontinuation, advise patient to resume fluid restriction and monitor changes in serum sodium and volume status

            Jynarque

            • If a dose is not taken at the scheduled time, take the next dose at its scheduled time

            Storage

            Tablets (Samsca): Store at 15-30°C (59-86°F)

            Tablets (Jynarque): Store at 20-25°C (68-77°F), excursions permitted between 15-30°C (59-86°F)

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            Samsca oral
            -
            30 mg tablet
            Samsca oral
            -
            15 mg tablet
            tolvaptan oral
            -
            30 mg tablet
            tolvaptan oral
            -
            15 mg tablet

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Patient Education
            tolvaptan oral

            TOLVAPTAN - ORAL

            (tol-VAP-tan)

            COMMON BRAND NAME(S): Samsca

            WARNING: Treatment with this drug should be started or restarted in a hospital for proper monitoring. If your level of sodium in the blood is raised too quickly, it may cause a serious (even fatal) condition called osmotic demyelination syndrome. The risk is higher if you have liver disease, poor nutrition, or if you use/abuse alcohol. Tell your doctor right away if you have symptoms such as trouble speaking/swallowing, mental/mood changes (such as confusion), weakness/involuntary movement in the arms/legs, or seizures.Do not use this medication to treat a certain kidney problem (autosomal dominant polycystic kidney disease-ADPKD). Due to the risk of serious liver damage, you must be in a special program for you to take this medication to treat ADPKD. Ask your doctor for details.

            USES: This medication is used to treat low levels of salt (sodium) in the blood, which can result from conditions such as heart failure and certain hormone imbalances. Tolvaptan belongs to a class of drugs known as vasopressin receptor antagonists. It works by increasing the amount of urine you make, causing your body to get rid of extra water. This helps to slowly increase to normal levels of salt in the blood.Different brands of this medication have different uses. Do not change brands of this medication unless directed by your doctor.

            HOW TO USE: Read the Medication Guide provided by your pharmacist before you start using tolvaptan and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth with or without food as directed by your doctor, usually once daily. You should not take this medication for longer than 30 days.To prevent dehydration, always have water ready to drink while taking tolvaptan. Drink when you are thirsty unless otherwise directed by your doctor.Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day. Do not stop and restart this medication on your own. You may need to go back to a hospital to restart this medication. Tell your doctor right away if you stop taking this medication for any reason.Avoid eating grapefruit or drinking grapefruit juice while using this medication unless your doctor or pharmacist says you may do so safely. Grapefruit can increase the chance of side effects with this medicine. Ask your doctor or pharmacist for more details.The dosage is based on your medical condition and response to treatment.

            SIDE EFFECTS: See also Warning section.Thirst, dry mouth, loss of appetite, constipation, or weakness may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Dehydration can occur. The risk is increased if you have vomiting or diarrhea that doesn't stop, and you cannot drink normally. Contact your doctor right away if you notice any symptoms of dehydration, such as fast heartbeat or dizziness/lightheadedness.People with severe liver disease (cirrhosis) may have increased risk of bleeding from the stomach or intestines while taking this medication. Tell your doctor right away if you have any of the following symptoms: black/bloody stools, vomit that contains blood or looks like coffee grounds.Tolvaptan may rarely cause serious (possibly fatal) liver disease. Get medical help right away if you have any symptoms of liver damage, such as: nausea/vomiting that doesn't stop, loss of appetite, stomach/abdominal pain, yellowing eyes/skin, dark urine.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Before taking tolvaptan, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: diabetes, liver disease, trouble urinating (such as due to enlarged prostate, blockage, inability to make urine), use/abuse of alcohol.To prevent dehydration while taking this medication, you must be able to replace fluids by drinking. Before taking this medication, tell your doctor if you are not able to drink normally or if you cannot feel if you are thirsty. (See also How to Use section.)This medication may rarely make your blood sugar rise, which can cause or worsen diabetes. If you have diabetes, check your blood sugar regularly as directed and share the results with your doctor. Your doctor may need to adjust your diabetes medication, exercise program, or diet.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: See also How to Use section.Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.A product that may interact with this drug is: desmopressin.Other medications can affect the removal of tolvaptan from your body, which may affect how tolvaptan works. Examples include azole antifungals (such as ketoconazole, itraconazole), boceprevir, cobicistat, HIV protease inhibitors (such as lopinavir, ritonavir), macrolide antibiotics (such as clarithromycin, erythromycin), ribociclib, rifamycins (such as rifabutin, rifampin), St. John's wort, drugs used to treat seizures (such as carbamazepine, phenytoin), telaprevir, among others.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

            NOTES: Do not share this medication with others.Lab and/or medical tests (such as levels of sodium/potassium in the blood) should be done while you are taking this medication. Keep all medical and lab appointments.

            MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

            STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

            Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.